This proposal requests funds for a Siemens MicroPET Focus 220 preclinical PET scanner in support of an existing positron emission tomography (PET) imaging research program that has been operational at the University of Pittsburgh since 1992. Dedicated small animal scanners such as the MicroPET Focus 220 significantly improve performance and reduce cost for imaging applications in animal models of disease compared with currently available clinical PET. Non- invasive in vivo imaging with microPET allows serial and longitudinal studies to be performed in the same animal giving researchers the opportunity to follow a single animal over time and to monitor the effects of interventions on disease progression and outcome. The Focus 220 will replace a legacy Concorde Microsystems (now Siemens) MicroPET P4 scanner installed in 2002, which has been declared end-of-life by the manufacturer and is no longer supported. The Pittsburgh MicroPET P4 system is unique in that it has been coupled with a small-bore 8-slice diagnostic CT (Neurologica, Inc. CereTom) providing intrinsically co-registered PET and diagnostic CT scans in larger research animals (e.g. non-human primates). This instrument is critical to several ongoing NIH-funded projects as well as a number of new projects under development that seek to leverage the unique multimodal capabilities of the Pittsburgh MicroPET P4/CereTom combination. The proposed MicroPET Focus 220 will replace the obsolete MicroPET P4 component of this hybrid preclinical PET/CT imaging system. In addition to providing a necessary replacement for the legacy MicroPET P4 scanner, several key features of the new MicroPET F220 platform have the potential to significantly enhance the ongoing PET research program. These include higher spatial resolution, increased and system sensitivity, and improved count-rate performance. If funded, this proposal will provide the necessary funds to replace the obsolete MicroPET P4 scanner with the current Focus 220 platform. This application describes 8 Major User and 3 Minor User projects that are currently NIH-sponsored and include a component of preclinical PET imaging. These projects will immediately benefit from this critical upgrade. Beyond the immediate impact, we expect that this upgrade will support further expansion of a very successful PET research program by providing continued support for preclinical PET and PET/CT imaging projects. PUBLIC HEALTH RELEVANCE: This proposal is for a preclinical microPET Focus 220 scanner for in vivo molecular imaging of animal models ranging in size from mice to non-human primates. In addition to PET-only scanning, it will be combined with a specialized CT, creating a PET/CT imaging platform geared toward larger research animals including non-human primates. This system will help facilitate basic science research, translational research and therapy development, from mouse models to larger animals, for wide variety of applications in, e.g., neuroscience, cancer, infectious and inflammatory disease, and transplant science.